Prostate cancer is the most diagnosed neoplasm in American males, and is the second leading cause of cancer related deaths in this group. The majority of these deaths are not a result of the primary tumor, but are directly attributed to the metastatic spread of the disease. For a cell to possess a metastatic phenotype it must undergo numerous changes. To metastasize a cell must, at a minimum, acquire the properties of: 1) anchorage independent growth; 2) increased motility; 3) decreased dependence on growth factors; 4) the ability to extravasate; 5) survivability in the circulatory system; 6) the ability to intravasate; and 7) growth in a target organ. Since these properties are functionally absent in non-metastatic cells and in cells of the host tissue, they are likely the result of genetic alterations or differences in gene expression. To better understand the metastatic process, it is imperative that genetic alterations involved in this process by elucidated. To this end, the Dunning rat prostate cancer tumor system has been used to identify differences in gene expression between the parental non- metastatic AT.1 tumor and its metastatic daughter tumor, the MAT-LyLu (MLL). Using a modification of the mRNA differential display technique, we have identified a gene, rPMET-1, that is over-expressed in the daughter MLL tumor when compared to its parent AT.1 tumor. The cDNA for this gene was sequenced, and a search for GenBank/EMBL revealed the sequence to be unique. The differential expression of this gene was confirmed by Northern analysis, and by relative quantitative polymer chain reaction. We hypothesize that rPMET-1 may have an important role in metastatic prostate cancer. Specifically, we propose to: 1) isolate the full length cDNA of rPMET-1, identified as being associated with metastatic prostate cancer, from a MLL-expression library, and clone it; 2) insert the full length cDNA into a transcription vector to generate the rPMET-1 protein and produce polyclonal antibodies to the generated protein; 3) elucidate the function of the rPMET-1 protein by studying its cellular and nuclear localization, and determine if a gene similar to rPMET-1 exists in human prostate cancer.